In vitro protection of 3-nitropropionic acid-induced toxicity of astrocytes by basic fibroblast growth factor and thrombin.
The protective action of basic fibroblast growth factor (bFGF) and thrombin on cultured cortical astrocytes in vitro to the toxic effects of 3-nitropropionic acid (3-NPA) was examined. 3-NPA produced concentration- and time-dependent astrocyte loss as indicated by decrease in the number of glial fibrillary acidic protein (GFAP) positive cells and increase in lactate dehydrogenase (LDH) level of the culture medium. The 3-NPA-induced cellular loss was apparent within 12 h and was maximal at 24 h. The presence of bFGF (10 ng/ml) by itself increased the number of astrocytes at various time intervals, and attenuated the 3-NPA-induced cell loss significantly at various concentrations (0.017-1.7 mM), in 24 and 48 h of exposure. Lower concentrations of thrombin (up to 1 nM) had no effect on the number of astrocytes but higher concentrations (10-100 nM) produced greater cell loss. Thrombin (1 nM) prevented the 3-NPA-induced decrease in GFAP positive cells at both 24 and 48 h intervals. This was further substantiated by the fact that thrombin as low as 0.01 nM attenuated the 3-NPA-induced increase of LDH activity at 24 and 48 h exposure times. But, with 1 nM of thrombin, the attenuation of the LDH activity was seen only at 24 h. The results indicate that 3-NPA produced acute astrocyte toxicity and was attenuated by bFGF and lower concentrations of thrombin.
Deshpande
S B
SB
Department of Physiology, Nagoya City University Medical School, Kawasumi 1, Mizuho-Cho, Mizuho-ku, Nagoya 467, Japan.
Nishino
H
H
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology*
D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D016222:Fibroblast Growth Factor 2; D007770:L-Lactate Dehydrogenase; D013917:Thrombin; C015392:3-nitropropionic acid